Jia Jia Huang

Blood lymphocyte-to-monocyte ratio identifies high-risk patients in diffuse large B-cell lymphoma treated with R-CHOP

Background Recent research has shown a correlation between immune microenvironment and lymphoma biology. This study aims to investigate the prognostic significance of the immunologically relevant lymphocyte-to-monocyte ratio (LMR), in diffuse large B-cell lymphoma (DLBCL) in the rituximab era. Methodology/Principal Findings We analyzed retrospective data from 438 newly diagnosed DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. We randomly selected 200 patients (training set) to generate a cutoff value for LMR by receiver operating characteristic (ROC) curve analysis. LMR was then analyzed in a testing set (n = 238) and in all patients (n = 438) for validation. The LMR cutoff value for survival analysis determined by ROC curve in the training set was 2.6. Patients with low LMR tended to have more adverse clinical characteristics. Low LMR at diagnosis was associated with worse survival in DLBCL, and could also identify high-risk patients in the low-risk IPI category. Multivariate analysis identified LMR as an independent prognostic factor of survival in the testing set and in all patients. Conclusions/Significance Baseline LMR, a surrogate biomarker of the immune microenvironment, is an effective prognostic factor in DLBCL patients treated with R-CHOP therapy. Future prospective studies are required to confirm our findings.

Comparison of entecavir and lamivudine in preventing hepatitis B reactivation in lymphoma patients during chemotherapy

Summary.  During chemotherapy for lymphoma, the administration of cytotoxic agents and rituximab often results in hepatitis B reactivation (incidence, 14–72%). This study was designed to compare the efficacy of entecavir and lamivudine in preventing hepatitis B reactivation in lymphoma patients. Between January 2007 and February 2009, patients treated in four hospitals in China were screened to identify those most appropriate for analysis. These patients received either entecavir or lamivudine during chemotherapy and for 6 months after completion of chemotherapy. A total of 34 patients received entecavir and 89 patients received lamivudine. Compared with the lamivudine group, the entecavir group had significantly lower rates of hepatitis (5.9 vs 27.0%, P = 0.007), hepatitis B reactivation (0 vs 12.4%, P = 0.024) and disruption of chemotherapy (5.9 vs 20.2%, P = 0.042). All patients with hepatitis B reactivation had B‐cell non‐Hodgkin’s lymphoma (stage III–IV). In lymphoma patients under chemotherapy treatment, entecavir is more effective than lamivudine in preventing hepatitis B reactivation. For patients with advanced stage disease, entecavir should be considered the primary preventive therapy.

Beclin 1 expression: A predictor of prognosis in patients with extranodal natural killer T-cell lymphoma, nasal type

Beclin 1 plays an important role in autophagy, differentiation, antiapoptosis and the development and progression of cancer. The function and expression of Beclin 1 in natural killer T-cell lymphoma is largely unexplored. The study aimed to investigate Beclin 1 expression and its relationship with prognosis in extranodal natural killer T-cell lymphoma, nasal-type (ENKL). Beclin 1 protein expression in 65 tumor specimens from patients newly diagnosed with ENKL was examined by immunohistochemistry (IHC). The clinical significance of Beclin 1 in ENKL was statistically analyzed. Immunopositivity for Beclin 1 was found in 56 (86.2%) of the 65 samples. Low Beclin 1 expression was significantly associated with advanced Ann Arbor stage, intermediate to high IPI risk and elevated LDH level. Low Beclin 1 expression was associated with worse overall survival (OS; p = 0.001) and progression-free survival (PFS; p = 0.017). In multivariate analysis, Beclin 1 expression, advanced Ann Arbor stage and B symptoms were found to be independent prognostic factors of OS and PFS. Consequently, a new clinico-pathological prognostic model was proposed. The model could discriminate different survival outcomes between low risk and high risk groups based on OS and PFS (p < 0.0001, respectively). Beclin 1 expression is predictive of prognosis in ENKL. The new clinico-pathological prognostic model may be help identify patients with different clinical outcomes.

Beclin 1 expression predicts favorable clinical outcome in patients with diffuse large B-cell lymphoma treated with R-CHOP

Beclin 1 plays a critical role not only in autophagy, but also in apoptosis and differentiation. The prognostic significance of beclin 1 in diffuse large B-cell lymphoma is largely unexplored. Immunohistochemical protein expression of beclin 1 in 118 tumor specimens from patients newly diagnosed with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone regimen from 2003 to 2007 was analyzed. Beclin 1 expression was observed in 101 (85.6%) patients. Low beclin 1 expression was related to B symptoms (P = .018), advanced Ann Arbor stage (P = .009), International Prognostic Index of 2 or higher (P = .049), elevated serum lactate dehydrogenase level (P = .037), and poor outcome using the revised International Prognostic Index model (P = .013). The complete remission rate after standard treatment was higher in patients with high beclin 1 expression than in those with low beclin 1 expression (77.5% versus 55.3%, P = .013). Beclin 1 expression was inversely associated with bcl-2 expression (P = .019) and positively associated with longer overall survival (P = .035) and progression-free survival (P = .013). In multivariate analysis, beclin 1 expression and the revised International Prognostic Index model independently predicted survival. The proposed clinicopathologic prognostic model including these 2 independent prognostic factors allowed classification of patients into 3 risk groups (P < .0001, respectively). Beclin 1 expression predicts superior clinical outcome in patients with diffuse large B-cell lymphoma treated with standard treatment. The novel prognostic model which divides patients with diffuse large B-cell lymphoma into different risk categories may help guide treatment planning.

Primary gastric non-Hodgkin's lymphoma in Chinese patients: clinical characteristics and prognostic factors

BackgroundOptimal management and outcome of primary gastric lymphoma (PGL) have not been well defined in the rituximab era. This study aimed to analyze the clinical characteristics, prognostic factors, and roles of different treatment modalities in Chinese patients with PGL.MethodsThe clinicopathological features of 83 Chinese patients with PGL were retrospectively reviewed. Staging was performed according to the Lugano staging system for gastrointestinal non-Hodgkins lymphoma.ResultsThe predominant pathologic subtype among Chinese patients with PGL in our study was diffuse large B cell lymphoma (DLBCL), followed by mucosa-associated lymphoid tissue (MALT) lymphoma. Among the 57 patients with gastric DLBCL, 20 patients (35.1%) were classified as the germinal center B cell-like (GCB) subtype and 37 patients (64.9%) as the non-GCB subtype. The 83 patients had a five-year overall survival (OS) and event-free survival (EFS) of 52% and 59%, respectively. Cox regression analysis showed that stage-modified international prognostic index (IPI) and performance status (PS) were independent predictors of survival. In the 67 B-cell lymphoma patients who received chemotherapy, 36 patients treated with rituximab (at least 3 cycles) had a mean OS of 72 months (95% CI 62-81) versus 62 months (95% CI 47-76) for patients without rituximab treatment (P = 0.021).ConclusionThe proportion of Chinese gastric DLBCL cases with non-GCB subtype was higher than the GCB subtype. Stage-modified IPI and PS were effective prognostic factors in Chinese patients with PGL. Our data suggested that primary gastric B-cell lymphoma might have an improved outcome with rituximab in addition to chemotherapy. More studies are necessary, preferentially large prospective randomized clinical trials to obtain more information on the impact of the rituximab in the primary gastric B-cell lymphoma.

Prognostic significance of peripheral monocyte count in patients with extranodal natural killer/T-cell lymphoma

BackgroundExtranodal natural killer/T-cell lymphoma (ENKL) has heterogeneous clinical manifestations and prognosis. This study aims to evaluate the prognostic impact of absolute monocyte count (AMC) in ENKL, and provide some immunologically relevant information for better risk stratification in patients with ENKL.MethodsRetrospective data from 163 patients newly diagnosed with ENKL were analyzed. The absolute monocyte count (AMC) at diagnosis was analyzed as continuous and dichotomized variables. Independent prognostic factors of survival were determined by Cox regression analysis.ResultsThe AMC at diagnosis were related to overall survival (OS) and progression-free survival (PFS) in patients with ENKL. Multivariate analysis identified AMC as independent prognostic factors of survival, independent of International Prognostic Index (IPI) and Korean prognostic index (KPI). The prognostic index incorporating AMC and absolute lymphocyte count (ALC), another surrogate factor of immune status, could be used to stratify all 163 patients with ENKL into different prognostic groups. For patients who received chemotherapy followed by radiotherapy (102 cases), the three AMC/ALC index categories identified patients with significantly different survivals. When superimposed on IPI or KPI categories, the AMC/ALC index was better able to identify high-risk patients in the low-risk IPI or KPI category.ConclusionThe baseline peripheral monocyte count is shown to be an effective prognostic indicator of survival in ENKL patients. The prognostic index related to tumor microenvironment might be helpful to identify high-risk patients with ENKL.

The glasgow prognostic score (gps) as a novel and significant predictor of extranodal natural killer/t-cell lymphoma, nasal type

The Glasgow Prognostic Score (GPS), an inflammation‐based prognostic score including C‐reactive protein and albumin, shows significant prognostic value in several types of solid tumors. The prognostic value of GPS in lymphoma remains unclear. We performed this study to evaluate the prognostic significance of GPS in extranodal natural killer (NK)/T‐cell lymphoma (ENKL). We retrospectively analyzed 164 patients with newly diagnosed ENKL. The prognostic value of GPS was evaluated and compared with that of International Prognostic Index (IPI), Prognostic Index for Peripheral T‐cell lymphoma unspecified (PIT), and Korean Prognostic Index (KPI). Patients with higher GPS tended to have more adverse clinical characteristics, lower rates of complete remission (P < 0.001), inferior progression‐free survival (PFS, P < 0.001), and inferior overall survival (OS, P < 0.001). Multivariate analysis demonstrated that high GPS, age > 60 years, and elevated LDH were independent adverse predictors of OS. GPS was found superior to IPI, PIT, and KPI in discriminating patients with different outcomes in low‐risk groups (all P < 0.05). GPS is an independent predictor of survival outcomes in ENKL. Inflammatory response might play an important role in the progression of ENKL and survival of patients with ENKL. Am. J. Hematol. 88:394–399, 2013.

Serum C-Reactive Protein (CRP) as a Simple and Independent Prognostic Factor in Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

Background C-reactive protein (CRP) is a biomarker of the inflammatory response, and it shows significant prognostic value for several types of solid tumors. The prognostic significance of CRP for lymphoma has not been fully examined. We evaluated the prognostic role of baseline serum CRP levels in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). Methods We retrospectively analyzed 185 patients with newly diagnosed ENKTL. The prognostic value of the serum CRP level was evaluated for the low-CRP group (CRP≤10 mg/L) versus the high-CRP group (CRP>10 mg/L). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were evaluated and compared with the newly developed prognostic model. Results Patients in the high-CRP group tended to display increased adverse clinical characteristics, lower rates of complete remission (P<0.001), inferior progression-free survival (PFS, P = 0.001), and inferior overall survival (OS, P<0.001). Multivariate analysis demonstrated that elevated serum CRP levels, age >60 years, hypoalbuminemia, and elevated lactate dehydrogenase levels were independent adverse predictors of OS. Based on these four independent predictors, we constructed a new prognostic model that identified 4 groups with varying OS: group 1, no adverse factors; group 2, 1 factor; group 3, 2 factors; and group 4, 3 or 4 factors (P<0.001). The novel prognostic model was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the low- and intermediate-low-risk groups, the intermediate-low- and high-intermediate-risk groups, and the high-intermediate- and high-risk groups. Conclusions Our results suggest that pretreatment serum CRP levels represent an independent predictor of clinical outcome for patients with ENKTL. The prognostic value of the new prognostic model is superior to both IPI and KPI.

High Ki-67 expression in diffuse large B-cell lymphoma patients with non-germinal center subtype indicates limited survival benefit from R-CHOP therapy.

Objectives:  Rituximab has significantly improved the survival of patients with DLBCL, especially those with non‐germinal center B‐cell‐like (non‐GCB) subtype. The impact of Ki‐67 expression, an index of proliferation, on the clinical outcomes of patients with DLBCL has largely been unexplored. This study aimed to investigate whether Ki‐67 expression is an indicator of outcome in DLBCL patients (especially non‐GCB DLBCL patients) treated with standard chemotherapy combined with rituximab.

Expression of BAFF and BAFF-R in Follicular Lymphoma: Correlation with Clinicopathologic Characteristics and Survival Outcomes

Background B-cell activation factor (BAFF) and BAFF-receptor (BAFF-R) play crucial roles in the viability and proliferation of malignant lymphoma cells. Limited information exists regarding expression profiles and the prognostic role of BAFF and BAFF-R in follicular lymphoma (FL). We sought to determine the expression profiles of BAFF and BAFF-R in FL and to evaluate the correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and outcome of FL. Correlation between expression levels of BAFF detected by immunohistochemical (IHC) and serum levels of BAFF was also evaluated. Methods Paraffin-embedded specimens from 115 patients were immunohistochemically examined for BAFF and BAFF-R expression. Expression levels were dichotomized into low versus high categories based on immunostaining intensity. The correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and patient outcome was assessed. Serum levels of BAFF in 35 of the 115 patients with IHC data were measured by Enzyme-linked Immunosorbent assay (ELISA). Results BAFF and BAFF-R were expressed in 88.7% (102/115) and 87.8% (101/115) of the cases, respectively. BAFF expression was significantly correlated with only one clinicopathologic feature: Ann Arbor stage. No significant correlation was found between expression levels of BAFF detected by IHC and serum levels of BAFF detected by ELISA. High expression of BAFF-R, but not BAFF, was significantly correlated with inferior progression-free survival (PFS; P = 0.013) and overall survival (OS; P = 0.03). High expression of BAFF-R, bulky disease, and elevated lactate dehydrogenase were correlated with inferior PFS and OS in multivariate analysis. A prognostic scoring system incorporating these 3 risk factors identified 3 distinct prognostic groups with 5-year PFS of 59.4%, 41.9%, and 10.7% and OS of 91.3%, 79.7%, and 45.8%, respectively. Conclusions Most patients with FL variably express BAFF and BAFF-R. High expression of BAFF-R, but not BAFF, may be an independent risk factor for PFS and OS in FL.